Methods to study tumor surveillance using tumor cell transplantation into genetically engineered mice.

When a tumor evolves, there is constant crosstalk between the transformed cells and cells of the immune system. Transplantation of well-established tumor cell lines into genetically engineered mice is a valuable tool to study the contribution of a gene of interest to tumor surveillance. These methods bear several advantages: first, such cell lines are well characterized; second, much data for reference exist; and third, the impact of the immune system can be separated from tumor cell intrinsic effects. Here, we provide protocols for tumor cell transplantations to address the role of a specific gene product in tumor surveillance. We furthermore describe several approaches to define the impact of natural killer cells and T cells, such as cell depletion and adoptive transfer experiments or use of different genetically modified mice.

Conditional ablation of TYK2 in immunity to viral infection and tumor surveillance.

Tyrosine kinase 2 (TYK2) has a pivotal role in immunity to infection and tumor surveillance. It is associated with several cytokine receptor chains including type I interferon (IFN) receptor 1 (IFNAR1), interleukin- (IL-) 12 receptor beta 1 (IL-12Rb1) and IL-10R2. We have generated a mouse with a conditional Tyk2 null allele and proved integrity of the conditional Tyk2 locus. TYK2 was successfully removed by the use of ubiquitous and tissue-specific Cre-expressing mouse strains. Myeloid TYK2 was found to critically contribute to the defense against murine cytomegalovirus. Ubiquitous TYK2 ablation severely impaired tumor immunosurveillance, while deletion in myeloid, dendritic or T cells alone showed no effect. The conditional Tyk2 mouse strain will be instrumental to further dissect TYK2 functions in infection, inflammation and cancer.